An experimental model has been employed to study the effects of immunotherapy with or without chemotherapy of the growth of established, measurable C3H mammary tumors. Utilzing C. parvum (CP) and cyclophosphamide (CY) tumor inhibition occurred to a greater degree when the agents were employed in combination than when either was administered alone. Investigations determined the optimal dosage, route, frequency and sequence of administration of this combination. In practically all experiments the effect on tumor growth varied despite the fact that tumors were from the same inoculum and were in syngneic hosts. Tumors either completely regressed, partially regressed, maintained constant volumes or progressively grew. Some totally regressed tumors recurred while still on therapy or after cessation of treatment. This model provides an opportunity to determine whether the disparate effect of treatment can be correlated with changes in tumor kinetics or in any of several selected host immune parameters which might exist prior to or occur during the course of therapy. Tumor response to therapy will be correlated with tumor kinetics (growth fraction, labeling index, DNA synthesis time, cell cycle time and cell loss factor) existent prior to and during the course of such therapy. In-vitro cytotoxicity testing and in-vivo neutralization of lymphnode and spleen cells, bone marrow cells, cultured macrophages and peripheral blood cells will be related to the response of tumors to therapy. The possibility that suppressor cells may be so related will be investigated. Serum will also be evaluated relative to humoral cytotoxicity as well as its ability to inhibit cellular cytotoxicity. Since most of the parameters can be evaluated simultaneously in the same mouse it may be possible to determine whether the success of treatment may be multifactorial (at least insofar as the parameters being measured are concerned). Since the set of studies relate to a variety of immune mechanisms they may indicate the direction in which additional exploration should proceed to determine the mechanism(s) responsible for successful therapy.